The purpose of this investigation is to examine the host-treponeme interaction and characterize the role of both humoral and cell-mediated immunity during the course of experimental Treponema pallidum infection in inbred guinea pigs. Guinea pigs infected intradermally with T. pallidum regularly develop darkfield positive lesions. We will determine when primary infection induces immunity to reinfection. At intervals when immunity is generated, lymphoid cells with or without serum from immune guinea pigs will be passively transferred to syngeneic uninfected recipients. Following this transfer animals will be challenged by intradermal inoculation of T. pallidum organisms. The subsequent development of darkfield positive skin lesions and local dissemination of treponemes to draining lymph nodes will be used to evaluate the degree of immunity to challenge infection. By selected depletion experiments the subpopulation of cell type rendering partial or full protection will be determined. Viable treponemes labelled with either 51Cr or 3H-adenine will be exposed in vitro to cells or serum obtained from T. pallidum infected/immune guinea pigs. Following specified culture periods anti-treponemal activity will be evaluated based on the release of labelled material from dying organisms or by the failure of damaged treponemes to incorporate radiolabelled compounds into newly synthesized nucleic acids. We will examine for the potential interference of intrinsic lymphocyte responses in vitro as well as the expression of protective immunity by a T. pallidum induced suppressor mechanism(s). These studies should enhance our understanding of some of the basic underlying immune mechanisms responsible for acquired protection against syphilitic infection which contribute to the destruction of pathogenic T. pallidum organisms or help explain the delay in effective anti-treponemal immune responses in the diseased host.